Evaluation of orellanine-induced toxicity from the mushroom Cortinarius orellanus and the antagonistic effect of Petroselinum crispum.

Mushroom poisoning is a worldwide public health problem that may cause serious toxic consequences on renal functions. The study aimed to evaluate the acute toxicity (24 h) of orellanine (OR) from Cortinarius orellanus in rat kidney and the ameliorative effect of parsley ethanolic extract. Twelve adult male Wistar rats were used to determine intraperitoneal (ip) median lethal dose (LD50) of OR, and 32 rats were divided into 4 groups (n = 8): OR group had 500 mg OR per kg bwt; OR + parsley group had the same dose of OR and after 1 h had 500 mg/kg parsley orally; parsley group had parsley only; and control had the vehicle 0.1% DMSO. Blood and kidney samples were collected at Hour 48. The LD50 dose was 1430 mg/kg for an observation period of 24 h. There were significant reductions (p < 0.01) in the body weight, and relative kidney weight of intoxicated rats compared to parsley treated rats and to controls. Similarly, this group had significantly higher levels of creatinine (p < 0.001), uric acid and urea (p < 0.05). The antioxidant glutathione peroxidase activity was significantly reduced (p < 0.01), while Cystatin C serum levels were significantly higher (p < 0.001) in the intoxicated untreated rats compared to all groups. Histopathological examination indicated necrotic damage in glomeruli and proximal tubules of rats given OR, which was relieved by parsley extract. Overall, the study showed that parsley extract ameliorated OR-induced kidney toxicity. This could be utilized in future research on adjunct therapy for toxicity-induced renal injury.

Antioxidant treatment and outcome of Cortinarius orellanus poisoning: a case series.

OBJECTIVES: To study the frequency, severity, and long-term outcome of renal injury in Cortinarius orellanus poisoning, to evaluate the association between the ingested amount of C. orellanus and outcome, and to evaluate the effect of N-acetylcysteine and corticosteroid treatment on outcome. METHODS: Case series of eight patients. Diagnosis and severity of acute kidney injury (AKI) and chronic kidney disease (CKD) were classified according to current AKI and CKD definitions. N-acetylcysteine and corticosteroids were administered to six patients, former according to the standard for paracetamol poisoning. MAIN FINDINGS: All patients developed AKI, six in the most severe stage and four required renal replacement therapy (RRT). After 12 months, seven patients presented with CKD, of whom three required chronic RRT and further two were in advanced CKD. AKI and CKD severity highly correlated with the consumed amounts of Cortinarius orellanus (r = 0.98, p < 0.001 and r = 0.78, p = 0.02, respectively) but not with N-acetylcysteine and corticosteroid treatment. CONCLUSIONS: AKI and CKD by current definitions and classifications are frequent and severe after Cortinarius orellanus poisoning. The ingested amount of Cortinarius orellanus correlates with the severity of both AKI and CKD. N-acetylcysteine and corticosteroid treatment do not seem to have a beneficial effect on either AKI or CKD.

Synthesis and antimalarial evaluation of a screening library based on a tetrahydroanthraquinone natural product scaffold.

As part of a research program aimed at discovering new antimalarial leads from Australian macrofungi a unique fungi-derived prefractionated library was screened against a chloroquine-sensitive Plasmodium falciparum line (3D7) using a radiometric growth inhibition assay. A library fraction derived from a Cortinarius species displayed promising antimalarial activity. UV-guided fractionation on the CH(2)Cl(2)/MeOH extract from this fungus resulted in the isolation of four known compounds: (1S,3R)-austrocortirubin (1), (1S,3S)-austrocortirubin (2), 1-deoxyaustrocortirubin (3), and austrocortinin (4). Compound 2 was used as a natural product scaffold in the parallel solution-phase synthesis of a small library of N-substituted tetrahydroanthraquinones (5-15). All compounds (1-15) were tested in vitro against P. falciparum 3D7 parasites and (1S,3S)-austrocortirubin (2), the major fungal constituent, was shown to be the most active compound with an IC(50) of 1.9 µM. This compound displayed moderate cytotoxicity against neonatal foreskin fibroblast (NFF) cells with an IC(50) of 15.6 µM.